Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts

This study was designed to test the hypothesis that cardiac myocytes have greater vulnerability to oxidative stress compared with cardiac fibroblasts.

The function of cardiac myocytes differs from that of fibroblasts in the heart, but differences in their response to oxidative stress have not been extensively studied.

Cardiomyocytes and fibroblasts from F344 neonatal rat hearts were cultured and exposed to different concentrations of hydrogen peroxide (H(2)O(2)) and menadione (superoxide generator). The mitogen-activated protein kinase (MAPK) proteins were assayed after oxidative stress; cell death was determined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electrophoresis.

The cardiac myocytes were significantly more vulnerable than the fibroblasts to oxidative damage, showing substantial DNA fragmentation and consistently poor cell survival after exposure to H(2)O(2) (100 to 800 microM), while the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 microM) and across increasing doses of H(2)O(2) (100 to 800 microM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H(2)O(2), but significantly more in cardiac fibroblasts. However, p38 MAPK and c-jun NH(2)-terminal kinase were phosphorylated more in the cardiac myocytes compared to cardiac fibroblasts. This was also the case after exposure to menadione.

Taken together, these results suggest that oxidative stress causes greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK family may partly mediate the observed differences in vulnerability and functional outcomes of the respective cell types.